Melasma is a common, acquired, symmetric hypermelanosis, characterized by irregular light to dark brown macules and patches commonly involving the cheeks, forehead, upper lip, nose, and chin 1.
The disease affects all racial groups, but is more prevalent in dark-complexioned individuals (skin types IV–VI), especially women of Hispanic descent who live in areas with intense ultraviolet radiation 2,3. An epidermal and a dermal type of melasma can be recognized, although frequently, there is a combination of the two types. Several therapeutic modalities, either alone or in combination, were studied 4. Therapies have included the routine use of sunscreens and various concentrations of hydroquinone (HQ) with or without the addition of tretinoin, salicylic acid, or glycolic acid (GA). In addition, azelaic acid, chemical peels, laser therapies 5, and recently tranexamic acid 6 have been used.
Chemical peels are a well-known modality for the treatment of melasma. The basic mechanism of the action of chemical peels in melasma is the removal of unwanted melanin by causing a controlled chemical burn to the skin 7. Chemical peeling agents have proved to be useful for the treatment of melasma both as a sole therapy and as an adjunct to other topical therapies. The aim of this study was to compare the efficacy and safety of chemical peeling using the modified Jessner’s solution versus GA 70% in the treatment of melasma in patients with different skin types.
Patients and methods
A total of 30 ambulatory Egyptian female patients with a clinical diagnosis of melasma on both cheeks with almost equal Melasma Area and Severity Index (MASI) scores 8 were enrolled from the Dermatology Outpatient Clinic, Alexandria University, between March 2011 and December 2011.
Participants with a history of hypertrophic scars or keloids, recurrent herpes infection, active dermatitis or unrealistic expectations, pregnant women, and women on oral contraceptive pills were excluded from the study. This study was approved by the Research Ethical Committee of Faculty of Medicine, Alexandria University, and an informed consent was obtained from each patient.
All participants were subjected to as assessment of history taking, general and dermatological examinations, and skin typing following the Fitzpatrick scale 9; Wood’s light examination was performed before treatment to determine the type of melasma (epidermal, dermal, or mixed) 10, and only patients with dermal type were excluded from the study. At the end of the treatment sessions, patient satisfaction score was assessed and an evaluation was performed by a blinded clinical investigator using the Global Aesthetic Improvement Scale (GAIS) 11. Photographs were taken at baseline and at the end of the treatment sessions. MASI scores of both treated sides of the face were calculated for each patient at baseline, at the end of the treatment sessions, and after the follow-up period of 16 weeks from the last session. Percentage of reduction in the MASI score was calculated after the last session.
The MASI score is calculated on the basis of the area of involvement, darkness of melasma, and homogeneity of hyperpigmentation. Four areas on the face were evaluated: forehead (f), right malar (rm), left malar (lm), and chin (c), which represent 30, 30, 30, and 10% of the facial skin, respectively. MASI was calculated for each half of the face separately. The area (A) of involvement in each of these four areas was assigned a numerical value 0–6 (0, no involvement; 1, 1–9%; 2, 10–29%; 3, 30–49%; 4, 50–69%; 5, 70–89%; and 6, 90–100%) 8. The severity of melasma was assessed on the basis of two factors: darkness (D) and homogeneity (H). These parameters were measured on a scale of 0–4 (0, absent; 1, slight melasma; 2, mild melasma; 3, marked melasma; and 4, maximum melasma). The equation used to determine MASI was as follows 8:
The following peeling agents were used in this study: GA (70%) (Enerpeel; Tebitech, Brescia, Italy) and the modified Jessner’s solution (Mesopeel Modified Jessner; Mesoestetic Pharma Group, Barcelona, Spain) composed of 8% citric acid (w/v), 14% lactic acid (w/v), 17% salicylic acid (w/v), and ethanol.
All participants were primed 2 weeks before starting the peel with adapalene 0.1% gel, HQ 4%, and sunblock with SPF more than 50. The face was degreased with acetone-soaked cotton. The modified Jessner’s solution was applied to the left side of the face and GA 70% was applied to the right side. Peeling agents covered the entire face without involvement of the angles of the eyes and mouth. The peeling agents were applied in two to three coats using two cotton-tipped applicators on a split-face basis until the appearance of frosting with modified Jessner’s solution or erythema with GA 70% with a maximum period of 5 min from peeling application. Then, neutralization was performed using sodium bicarbonate 30%.
All patients were instructed to apply a mild corticosteroid cream for 2 days after the procedure and to apply an emollient continuously until the next session. Also, they were strictly instructed to limit sun exposure during therapy with application of a sunblock with SPF more than 50.
Peeling sessions were scheduled every 2 weeks. Sessions were repeated for a maximum of eight sessions. Side effects were recorded during every session by asking the patient about what she felt after the last session and observing whether any problem could still be seen on the face. After the last treatment session, all the patients included were instructed to avoid sun exposure and to apply sunscreen (SPF>50) during the follow-up period.
Data were analyzed using the SPSS software package (version 18.0; SPSS Inc., Chicago, Illinois, USA). Data were expressed using range, mean, SD, and median. Comparisons of abnormally distributed paired data between both sides of the face and between before and after results in each individual were analyzed using the Wilcoxon signed-rank test. The P value was assumed to be significant below 0.05.
The age of the patients ranged between 22 and 64 years, mean age 44.633±8.552 years. The duration of the lesion ranged from 1 to 17 years, mean 5.067±3.685 years. Nineteen (63%) patients were of skin type III. Six patients were of skin type II, three patients were type IV, and two patients were of skin type V. Wood’s lamp examination showed that 17 (57%) cases were of the epidermal type and 13 (43%) cases were of the mixed type. Out of the 30 patients included, 18 completed the eight sessions, whereas 12 completed only six sessions as they reached grade 4 by GAIS assessment by the physician and/or optimal cosmetic result (score 3) by the patient satisfaction score. However, only six patients were lost during the follow-up period and 24 patients completed the 16 weeks.
Comparison of the Melasma Area and Severity Index score between the right (glycolic acid 70%) and the left (modified Jessner’s) sides of the face
The mean MASI score before treatment was 6.91±2.3 for the right side of the face and 6.62±1.96 for the left side of the face. After the end of the treatment sessions, the mean MASI score was reduced to 1.73±1.42 for the right side and to 1.52±1.42 for the left side. The mean score reduction was significantly more on the left side compared with the right side of the face (P=0.03). At the end of the follow-up period, there was a nonsignificant difference in the mean MASI scores on both sides of the face compared with that at baseline. Meanwhile, at the end of the follow-up period, there was a significant increase in the MASI score on the right side compared with the left side of the face (P=0.02) (Table 1).
Mean percentage reductions in Melasma Area and Severity Index scores in different skin types on both sides of the face
After the last treatment session, in patients with skin type III (Fig. 1), there was a significant reduction in the MASI score on the left side compared with the right side of the face (P=0.012). In patients with skin type IV, there was a nonsignificant reduction in the MASI score on the right side compared with the left side of the face after the last session (P=0.180). There was a nonsignificant difference in the MASI score between both sides of the face in patients with skin types II and V (Figs 2 and 3). At the end of the follow-up period, there was a significant increase in the MASI score on both sides of the face compared with that at the end of the treatment sessions in all skin types (Table 2).
Patient satisfaction and physician evaluation
For the overall procedure, of the 30 patients, 19 (63%) were fully satisfied, 10 (3.3%) were moderately satisfied, and one (4%) was slightly satisfied. In terms of patient satisfaction for each side of the face separately, there was a nonsignificant difference between both sides. Meanwhile, in the GAIS evaluated by a blinded physician, there was a nonsignificant difference in all scores, except in scale 4 (very much improved: optimal cosmetic result), which was significantly higher for the left side than for the right side (P=0.03) (Table 3).
Postinflammatory hyperpigmentation (PIH), erythema, discomfort, dryness, folliculitis, and swelling were the common side effects, with a nonsignificant difference between both sides of the face (P>0.05) (Fig. 4). PIH was recorded in five cases (four of them were of skin types IV and V); three (10%) of them on the GA-treated side compared with two (6.7%) cases on the modified Jessner’s-treated side. Erythema, discomfort, and swelling were mild and transient, and resolved in a few days.
In the present study, 63% of the melasma patients were of skin type III, and three no patients with skin types I and VI in this study. Trichloroacetic acid (TCA) peel is a commonly used peel in lighter skin, but less frequently preferred in darker skin types because of the risk of scarring and postpeel dyschromias. This is probably because frosting, the end point for a TCA peel, is not well tolerated in darker skin, and hence can lead to overtreatment 12. According to the current levels of evidence and the strength of recommendations for various peeling agents for dark skin, GA peels have been proven to be the best both in terms of safety as well as efficacy 13. In the current study, the significant reduction in the MASI score in the GA-treated side was in agreement with many of other previous studies that reported the efficacy of GA in the treatment of various forms of hyperpigmentation 13,14.
There is a paucity of studies using the modified Jessner’s solution as a sole peeling agent in the treatment of melasma. The modified Jessner’s solution is different from the classic Jessner’s solution because it does not contain resorcinol; thus, it has the advantage of avoiding the possible allergic reaction and hyperpigmentation problems, which may be induced by resorcinol in the classic Jessner’s, especially in skin types V and VI 15. In the present study, the significant reduction in the MASI score in modified Jessner’s solution-treated side compared with the GA-treated side after the last session and at the end of the follow-up period, especially in skin type III, compared with GA-treated sides, could be explained by the fact that the modified Jessner’s solution is composed of three acids; acting together in a single peeling agent, they will exert a synergistic action that may reach the level of the papillary dermis 16, which is a deeper level for peeling compared with GA, which decreases corneocytes’ cohesion, leading to sloughing of dead cells 17. The increase in the mean percentage of the MASI score at the end of the follow-up period on both sides could be explained by recurrence of melasma because of either noncompliance of patients for strict sunscreen application or insufficiency of sunscreens alone as maintenance therapy. To solve this problem, previous studies reported the importance of applying a triple combination (HQ, tretinoin, and fluocinolone acetonide) regimen for 6 18 or 12 19 months after melasma resolution to avoid recurrence.
Comparing a 15% TCA peel alone in one side and in combination with modified Jessner’s solution to the other side in patients of skin type II and IV, Safoury et al. 12, found a significant reduction in the MASI score in the side treated by a combination of TCA and modified Jessner’s solution as compared with the TCA alone-treated side. They suggested that this difference could be attributed to the addition of the modified Jessner’s peel.
In the present study, only patients with skin type II showed better response to GA than modified Jessner’s solution, although the difference was not significant. This observation may be because of the fact that the skin response to GA in younger individuals is better than that in older individuals 13. Meanwhile, in the current study, there was a better response in patients with skin types IV and V to the modified Jessner’s solution than to GA 70%, but the difference in the MASI score was not significant.
Lawrence et al. 20 used the split-face method to compare the efficacy of GA 70% versus classic Jessner’s solution on dark-skinned patients (skin types IV through VI). They found that there was no significant difference between the two peeling agents in their patients. They reported that the poor response of the darker skin to the peeling agents may be attributed to the irritation caused by GA 21; also, they are susceptible to PIH. This may be because of higher incidence of PIH in individuals with dark skin types. In terms of the safety and side effects reported, PIH was the most troublesome side effect, especially in patients with skin type IV. This could be explained by the irritation that occurs because of the application of the acids on darker skin. Safoury et al.12 found that the combination of modified Jessner’s solution with TCA (15%) in the treatment of melasma decreased the risk of PIH that occurs commonly in dark-skinned individuals following the TCA peel.
In another study, Khunger et al. 21 reported discomfort, persistent erythema, and swelling, suggesting that 70% GA is more irritating and less tolerated than 1% tretinoin peels in darker-skinned patients. This was in contrast to Kalla et al. 22 who found that 55–75% GA was not associated with local irritant reactions compared with a 10–15% TCA peel in patients with skin types III–V. The incidence of side effects was higher on the GA-treated sides. This may be attributed to the fact that the action of α-hydroxy acids is time dependent 15; thus, the longer the duration of contact with the skin, the greater the effect as well as higher the incidence of side effects. However, in this study, the difference in the incidence of side effects between both sides was not significant, indicating almost equal safety profiles of both peeling agents. A recent evidence-based review found that triple-combination topical therapy for melasma was the most effective, but ∼40% of patients develop erythema and peeling 23. Another evidence-based analysis 24 suggested that the use of lasers for the treatment of melasma cannot be recommended because of unpredictable safety and efficacy. Chemical peel, laser, and light therapies produced mixed results, with an increased risk of irritation and subsequent hyperpigmentation, particularly in darker-skinned individuals 23.
In conclusion, determination of patient skin type could aid the choice of a proper peeling agent for the treatment of melasma. Although both modified Jessner’s and GA are effective and safe for the treatment of melasma, modified Jessner’s solution is more effective for the treatment of melasma in patients with different skin types, especially skin type III, with higher patient satisfaction. After the treatment of melasma patients by any therapeutic tools, patients should receive maintenance treatment not only with proper sunscreen but also with topical depigmenting agents to avoid recurrence.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2014 Egyptian Women's Dermatologic Society
glycolic acid; Jessner’s solution; melasma